The present invention relates to an efficient carbonate synthesis by way of cesium carbonate promoted alkylation of various alcohols with organic electrophiles in the presence of carbon dioxide. In particular, the invention relates to the alkylation of aliphatic alcohols with alkyl halides.
Organic carbonates exhibit unique physical and chemical properties, accommodating a variety of applications. For example, carbonate functionalities have been used as protecting groups or intermediates in numerous syntheses. They have also been utilized as synthetic intermediates in functional transformations and functional group manipulations such as ester formation, glycosylation, urethane synthesis, linker preparation on solid phase synthesis, and so on. Alkylation with alkyl carbonates is also a prominent application in synthesis.
Organic carbonates have been used as fuel additives, (gasoline, diesel and so on), dyes, and lubricating oils, (for example, in refrigerators). Mixed carbonate ester derivatives of quinophthalone dyes have been prepared and utilized for thermal imaging. Carbonate has been used as a bridging member between anthraquinone dyestuffs and synthetic organic fibers, especially polyethylene glycol terephthalate fibers.
Some carbonates have been used as polymerization catalysts. For example, diethyl carbonate catalyzed propylene polymerization while isocynates were polymerized with polyols in the presence of a catalytic amount of an organic carbonate salt. More importantly, numerous organic carbonates are used as monomers for various polymerization. Typical examples encompass cyclic carbonates such as trimethylene carbonate as well as acyclic carbonates including diethylene glycol bis(allyl carbonate), (DADC).
Carbonates are also very important in the polymer industry. For example, DADC is widely used as a polymerization monomer for the production of an optical plastic in the manufacturing of lenses, safety glasses, guards, watch glasses, and instrument windows.
Aliphatic carbonates or carbonate functionalities have shown pharmacologic activities including protein kinase inhibition, antibacterial activity, and stimulatory effect on the central nerve system.
Carbonates often play an important role in pharmacology as demonstrated by 6xe2x80x2-carbonate esters of zearalanol promoting growth in ruminants and also reducing the severity of vasomotor symptoms associated with menopause in women.
Biodegradable organic carbonates have been implemented in medicinal fields as prodrugs, drug delivery materials, sutures, surgical implant materials, and so on. Some carbonate polymers, resistant to biodegradation, are strongly believed to provide good materials for artificial skin and bone structure.
Thus, in view of the vast and increasingly important role played by carbonates, a protocol for efficient carbonate synthesis is desirable.
Common methods leading to carbonates are categorized into alcoholysis of phosgene or its derivatives, organic carbonate exchange, carbon dioxide alkylation, and inorganic carbonate alkylation. These methods employ the usage of strongly basic conditions, special carriers, or catalysts, and elevated temperatures or pressures. In addition, the bases used, such as potassium carbonate and organic amines, require high temperatures (i.e., 80xc2x0 C.) and/or lengthy reaction times (i.e., 20 hours).
Thus, known methods for the syntheses of alkyl carbonates have shortcomings including the following:
1. Use of toxic or expensive reagents such as phosgene and silver salts. 2. Employment of harsh reaction conditions such as high temperature and pressure. 3. Low yields due to the inconvenient and inefficient processes. 4. Difficulties in purification because of the complicated product mixture.
5. Limitations in compatible and available substrates.
Above all, the existing methods such as alcoholysis of phosgene or its derivatives, organic carbonate exchange, carbon dioxide alkylation and inorganic carbonate alkylation lack in generality for the carbonate synthesis, especially unsymmetrical aliphatic carbonates. Although carbonate exchange methodologies provide mixed alkyl carbonates, the desired products are part of the statistical mixtures, making these syntheses inapplicable to practical utilities.
A need therefore exists for an improved process for the synthesis of carbonates which avoids the aforementioned disadvantages and drawbacks.
It is therefore an object of the present invention to provide an improved process for the synthesis of carbonates which avoids the aforementioned disadvantages and drawbacks.
It is a further object of the present invention to provide a process that obviates the use of toxic or expensive reagents.
It is a further object of the present invention to provide a process that obviates harsh reaction conditions.
It is a further object of the present invention to provide improved and purer carbonate yields.
It is a further object of the present invention to provide a methodology for synthesizing new biomolecules.
It is a further object of the present invention to provide new polymerization materials.
It is a further object of the present invention to provide carbonate synthesis methods that are facile on solid phase, contributing to the generation of a wide variety of alkyl carbonate libraries.
Reported herein is the efficient synthetic protocol for mixed alkyl carbonates, which are generated by cesium carbonate promoted O-alkylation of various aliphatic alcohols with alkyl halides in the presence of carbon dioxide. Unlike the known methods, these methodologies utilize two different coupling partners and prepare the unsymmetrical alkyl carbonates selectively. Use of cesium base is preferred for the intended transformation and the reaction conditions are mild, e.g., room temperature and atmospheric pressure. Employment of tetrabutylammonium iodide is also preferred in certain cases to yield efficient and rapid synthesis. This technology is successfully applied to the synthesis of symmetric carbonates. As in the solution phase, all these methods are facile on solid phase, contributing to the generation of a wide variety of alkyl carbonate libraries.